Background: In patients with chronic obstructive pulmonary disease (COPD), acute exacerbations affect patients' health and can lead to death. This study was aimed to develop a prediction model for in-hospital mortality in patients with acute exacerbations of COPD (AECOPD). Method: A retrospective study was performed in patients hospitalized for AECOPD between 2015 and 2019. Patients admitted between 2015 and 2017 were included to develop model and individuals admitted in the following 2 years were included for external validation. We analyzed variables that were readily available in clinical practice. Given that death was a rare outcome in this study, we fitted Firth penalized logistic regression. C statistic and calibration plot quantified the model performance. Optimism-corrected C statistic and slope were estimated by bootstrapping. Accordingly, the prediction model was adjusted and then transformed into risk score. Result: Between 2015 and 2017, 1,096 eligible patients were analyzed, with a mean age of 73 years and 67.8% male. The in-hospital mortality was 2.6%. Compared to survivors, non-survivors were older, more admitted from emergency, more frequently concomitant with respiratory failure, pneumothorax, hypoxic-hypercarbic encephalopathy, and had longer length of stay (LOS). Four variables were included into the final model: age, respiratory failure, pneumothorax, and LOS. In internal validation, C statistic was 0.9147, and the calibration slope was 1.0254. Their optimism-corrected values were 0.90887 and 0.9282, respectively, indicating satisfactory discrimination and calibration. When externally validated in 700 AECOPD patients during 2018 and 2019, the model demonstrated good discrimination with a C statistic of 0.8176. Calibration plot illustrated a varying discordance between predicted and observed mortality. It demonstrated good calibration in low-risk patients with predicted mortality rate <= 10% (P = 0.3253) but overestimated mortality in patients with predicted rate >10% (P < 0.0001). The risk score of 20 was regarded as a threshold with an optimal Youden index of 0.7154. Conclusion: A simple prediction model for AECOPD in-hospital mortality has been developed and externally validated. Based on available data in clinical setting, the model could serve as an easily used instrument for clinical decision-making. Complications emerged as strong predictors, underscoring an important role of disease management in improving patients' prognoses during exacerbation episodes.